Lipase-catalyzed enantioselective synthesis of methyl (R)- and (S)-2-tetradecyloxiranecarboxylate through sequential kinetic resolution

Among a variety of lipases tested, Pseudomonas fluorescens lipase has been found to induce enantioselective acylation of methyl (R,S)-2-hydroxy-2-(hydroxymethyl)hexadecanoate (3), affording, through sequential kinetic resolution, both enantiomers in good optical yields. Efficiency of the process has been compared to the Sharpless asymmetric dihydroxylation of alkene 2 using (DHQD)(2)PHAL and (DHQ)(2)PHAL as chiral ligands. The (R)- and (S)-3 enantiomers have been cyclized to afford both enantiomers of methyl 2-tetradecyloxiranecarboxylate (1), a potent hypoglycemic agent and inhibitor of long-chain fatty acid oxidation.